Long-term systemic treatment with lysergic acid diethylamide causes retinal damage in CD1 mice.

As a classical hallucinogen with high potential for abuse, lysergic acid diethylamide (LSD) can cause long-lasting abnormalities in retina, but little is known about the exact mechanism. This study was to investigate effects of long-term systemic treatment of LSD at low dose on retinal damage and understand the underlying mechanisms. CD1 mice were treated intraperitoneally with 0.1 mg/kg or 0.2 mg/kg LSD daily for 2 months, mice treated with saline as negative control. Electroretinography (ERG) was used to test the retinal function after LSD treatment. Hematoxylin and eosin staining was used to show the retinal morphology and evaluate the loss of photoreceptor cells. Terminal deoxynucleotidyl transferase dUTP Nick end labeling (TUNEL) assay was used to detect the apoptotic cells. Enzyme-linked immunosorbent assays were used to show the oxidative stress and inflammatory response. Real-time PCR and western blot were applied to measure the gene and protein change to explore the underlying mechanisms. Results demonstrated that 2 months treatment with LSD caused retinal damage, evidenced by decreased ERG response and increased apoptotic photoreceptor cells through increasing oxidative stress and inflammatory response. Our study indicated that long-term systemic administration of LSD caused neurotoxic effects on retinas of CD1 mice, suggesting the potential mechanisms for the retina damage caused by LSD abuse.